Trovafloxacin is a new fluoroquinolone that achieves high concentrations in tissues and has a relatively short half-life. This study assessed its effectiveness in clearing chlamydial infection of the cervix. Twenty-four monkeys were randomly assigned to one of four treatment groups ( n=6 per group). Each monkey received 3-5 weekly cervical inoculations with Chlamydia trachomatis. Cervical samples for culture and ligase chain reaction (LCR) were collected weekly throughout the study to document infection. One week after the final inoculation, treatment was initiated (trovafloxacin (7d, doxycycline (7d, azithromycin (1d or placebo). One week after completion of therapy, cervical biopsies were collected for histopathological assessment and for determination of antibiotic tissue levels. Vaginal swabs for microbiological analysis were collected at baseline, immediately before treatment, and one week after completion of treatment. All animals tested positive for chlamydial infection by culture and LCR before initiation of treatment. All of the monkeys treated with trovafloxacin cleared infection (100%), as did 100% of those treated with doxycycline, versus 66% treated with azithromycin and 50% receiving placebo. Histopathology of cervical tissues revealed the worst inflammatory infiltrate in untreated monkeys (as expected), slightly less severe pathology in those treated with doxycycline, and less still in those treated with azithromycin and trovafloxacin. In a subset of monkeys whose upper reproductive tract tissues were collected, trovafloxacin treatment was associated with much healthier looking tissues than any other treatment group. The vaginal flora remained largely unchanged in all animals. Trovafloxacin appears to be as effective as doxycycline in its ability to clear chlamydial infections of the cervix without harming the cervicovaginal environment. Trovafloxacin may preserve upper reproductive tract tissues from chlamydial damage better than currently available therapies.